lacnotuzumab (MCS110)

Pexidartinib is the first CSF-1 receptor inhibitor approved for the treatment of TGCT. Here, we discuss various available treatment strategies and ongoing investigations and trials targeting diffuse TGCT, which include nilotinib, lacnotuzumab, cabiralizumab, vimseltinib, and emactuzumab.

MCS110 in combination with dabrafenib and trametinib was reasonably well tolerated in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration.

P1, N=64, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; This was a sponsor decision and was not a consequence of any safety concern

P1, N=64, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2022 --> Feb 2023 | Trial primary completion date: Oct 2022 --> Feb 2023

P1, N=64, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2022 --> Oct 2022 | Trial primary completion date: Jun 2022 --> Oct 2022

P1, N=64, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=220 --> 64 | Trial completion date: Jan 2022 --> Jun 2022 | Trial primary completion date: Jan 2022 --> Jun 2022

Despite successful target engagement and anticipated pharmacokinetic profile, lacnotuzumab+gem-carbo showed comparable antitumor activity to gem-carbo alone, with slightly poorer tolerability. However, the data presented in this manuscript would be informative for future studies testing agents targeting the CSF-1-CSF-1R pathway in TNBC.

Flow cytometric, circulating total CSF1 in plasma and gene expression profiling results demonstrated that targeting CSF-1 with lacnotuzumab in the periphery and tumor microenvironment leads to decrease in monocytes and reduced expression of macrophage associated genes in patients with advanced cancers. Unfortunately, in the heavily pretreated patient populations studied in this trial, only a limited clinical efficacy was demonstrated.

P2, N=50, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Jul 2020 --> Mar 2020 | Trial primary completion date: Jul 2020 --> Mar 2020

P2, N=50, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2020 --> Jul 2020 | Trial primary completion date: Dec 2019 --> Jul 2020

P1, N=220, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2020 --> Jan 2022 | Trial primary completion date: Oct 2020 --> Jan 2022